[C:1]([NH:5][C:6](=[O:15])[C:7]1[CH:12]=[CH:11][C:10](Br)=[CH:9][C:8]=1[F:14])([CH3:4])([CH3:3])[CH3:2].[NH2:16][C:17]([CH3:22])([CH3:21])[C:18]([OH:20])=[O:19].C([O-])([O-])=O.[K+].[K+].C(C1CCCCC1=O)(=O)C.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C.[Cu]I.O>[C:1]([NH:5][C:6]([C:7]1[CH:12]=[CH:11][C:10]([NH:16][C:17]([CH3:22])([CH3:21])[C:18]([OH:20])=[O:19])=[CH:9][C:8]=1[F:14])=[O:15])([CH3:4])([CH3:3])[CH3:2]The title compound, made in accordance with General Method 3, may be used to prepare compound 3 in accordance with General Method 1. N-tert-Butyl-4-bromo-2-fluorobenzamide (850 mg, 3.1 mmol), 2-aminoisobutyric acid (450 mg, 4.36 mmol), CuI (100 mg, 0.5 mmol), TEA (0.2 mL) and K2CO3 (1.0 g, 7.2 mmol) were charged in DMF (8 mL) and water (2 mL) and stirred at RT for 5 min. 2-Acetylcyclohexanone (100 mg, 0.7 mmol) was added and the reaction mixture was heated at 100° C. for 18 h. The reaction mixture was acidified with 1 M citric acid (pH 4) and extracted with ethyl acetate (50 mL, 2 times). The combined organic layer was dried over Na2SO4 and concentrated to obtain 1.0 g of 2-(4-(tert-butylcarbamoyl)-3-fluorophenylamino)-2-methylpropanoic acid.
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